1. Field of the Invention
The invention relates to sample dispensing systems and, more particularly, to the delivery of liquid samples onto substrate, such as a microarray, for laboratory analysis.
2. Description of the Background Art
Genetic sequencing efforts, such as the Human Genome project, have produced vast amounts of information for basic genetic research that have proven useful in developing advances in health care and drug research. These advances are possible because of improvements in engineering and instrumentation that provide advanced tools for the biotechnology community to continue with basic genetic research. With these advances, scientists can move from basic genomic discoveries to associating specific phenotypes and diseases, and can thereby better identify targets for drug development.
Nucleic acid sequencing and diagnostic methods often analyze samples deposited onto target locations on substrates microarrays, such has microplates, silicon chips and other such supports capable of retaining biological molecules or samples at discrete loci. Microarrays have been used to execute tests on large batches of genetic samples to generate phenotype associations and improve interpretation of the large data sets that result from such tests. A typical microarray, referred to as a chip, includes a substrate, such as a silicon or silicon-coated substrate, on which a large number of reactive points receive samples for testing. Microarray chips provide a technology that permits operators to increase sample throughput, allowing the screening of large numbers of samples and reducing reagent costs by using submicroliter sample volumes. Preparation of such arrays employs a variety of methodologies, including printed arrays and spotted arrays, with a wide variety of substrate surfaces and different modes of quantification. The resulting microarrays are used as substrates for a variety of biochemical applications.
Among the ways for delivery of multiple samples to loci on microarray surfaces are solid pins. The solid pins typically are dipped into a liquid sample, which coats the tip of each pin, holding a sample droplet by surface tension. The coated pins are then touched to a target surface on a microarray substrate, so that the sample is transferred to the target by contact printing. The size and taper of the pin tool tip can affect the volume of liquid sample that is picked up during dipping. The amount of liquid sample transferred on contact will vary with the surface tension of the liquid. Pin tools also can be problematic for high throughput systems because the pins may have to be changed if different sample volumes are desired, or if the nature of the liquid sample is changed to avoid sample contamination. In addition, pin tools cannot be used in situations where contact dispensing where there is a risk of damage to a fragile preloaded sample, such as for mass spectrometric analyses in which samples are deposited on loci that have preloaded material, such as matrix material for matrix-assisted laser desorption (MALDI).
Some mass spectrometry formats, such as MALDI formats, combine the sample to be tested with a matrix material, such as an inorganic acid, which when dried forms a crystal structure. Matrix material can be preloaded on a mass spectrometry substrate and the sample can be added at a later time, using an appropriate liquid dispensing apparatus. When a sample target is preloaded or prespotted with the porous matrix material required for mass spectrometry, direct contact by the solid pin with the matrix material can crush the material.
Other liquid samples dispensing apparatus rely on piezoelectric mechanisms, sometimes using quill-type pin tools that hold the samples in a cut-out at the lower tool tip. Such piezoelectric delivery systems are susceptible to dispensing satellite droplets on a target location because of surface tension effects. Piezoelectric systems also may be prone to variations in voltage and frequency among different tips, which results in variation between the volume of liquid sample dispensed from different individual tips.
From the discussion above, it is apparent that there is a need for a dispensing systems that can accurately deposit precise amounts of liquid sample on target locations on a substrate, with a high throughput rate, without risk of cross contamination of samples or damage to the deposited material. Therefore, it is an object herein to provide apparatus, methods and substrates for fulfilling these and other needs.